Accuracy of telomerase in cervical lesions: a systematic review

Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
International Journal of Gynecological Cancer (Impact Factor: 1.96). 11/2007; 17(6):1205-14. DOI: 10.1111/j.1525-1438.2007.00980.x
Source: PubMed

ABSTRACT The detection of telomerase activity in cervix may provide information on cervical carcinogenesis and may be a marker to monitor cervical intraepithelial neoplasia transition. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Ten studies were analyzed, which included 1069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9-5.6). The DOR for a positive telomerase test for high-grade squamous intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1-10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2-91). Our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions.

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    ABSTRACT: Human papillomavirus (HPV) has been estab- lished as an important etiological factor for the development of cervical cancer. This DNA virus primarily infects the epithelium and can induce benign and malignant lesions of the mucous membranes and skin. Some HPVs are considered high risk due to their role in ma- lignant progression of cervical tumors. Genital HPV infections are common and usually tran- sient among young sexually active women. Only a small fraction of infected women devel- op cervical cancer, implying the involvement of environmental and genetic cofactors in cer- vical carcinogenesis. Classification, virology, pathology, natural history, epidemiological features of genital HPV infection, and future prospects for cervical cancer prevention with HPV vaccines will be reviewed here.
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    ABSTRACT: The unique ability of tumour cells to proliferate indefinitely is crucial to neoplastic progression as it allows these cells to express the aggressive properties of cancer without the censure of physiological ageing. This is in contrast to normal somatic cells which are subject to a "mitotic clock," a phenomenon that has been linked to telomeric shortening after each round of cell replication, so that eventually the loss of genetic material reaches a critical stage and the cells undergo senescence and cell death. A study was conducted to investigate the role of telomerase, an RNA-containing enzyme that restores the telomere length, in the neoplastic cell immortalization and progression process. Fresh human tissue samples taken from excision specimens received by the Department of Pathology, University of Malaya Medical Centre, were investigated for telomerase activity using a commercial Telomerase PCR-ELISA kit (Boehringer Mannheim). Specimens comprised 33 breast lesions (10 infiltrating breast adenocarcinoma, 13 fibroadenoma and 10 non-neoplastic breast tissue), 27 colonic lesions (17 colonic adenocarcinoma and 10 non-neoplastic colonic mucosa) and 42 cervical lesions (20 cervical carcinoma and 22 non-neoplastic cervical tissues). Telomerase activity was found in 6 (60%) of 10 breast carcinomas, 6 (46%) of 13 fibroadenomas, none of the 10 nonneoplastic breast samples, 3 (17.6%) of 17 colon carcinomas and none of the 10 non-neoplastic colonic mucosal samples, 12 (60%) of 20 cervical carcinoma and 3 (13.6%) of 22 non-neoplastic cervical samples. 5/10 (50%) Stage I, 4/7 (57%) Stage II, 2/2 (100%) Stage III and 1/1 (100%) Stage IV cervical carcinomas showed telomerase activity. These findings support a contributory role for telomerase in tumourigenesis with activation occurring from neoplastic transformation and increasing with tumour progression.
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    ABSTRACT: Cervical cancer is the second type of women cancers, most cases being reported in the developing countries where it represents the main cause for mortality in women. The aim of this study was to clarify the role of hTERT expression levels in cervical carcinogenesis, in each type of cytological diagnostic group (normal/inflammatory, ASCUS, LSIL, HSIL, cancer groups) like potential diagnostic marker. Methods: The smears obtained from 50 women with/without suggestive HPV infection pathology were cytological investigated. The viral testing was based on the presence of HPV DNA using the IINNOLIPA kit and semi-quantitative expression levels of hTERT were estimated in RT-PCR. Results: HPV was present in 84% of the examined cases, but only in 40.48% of them hTERT expression was observed. hTERT mRNA was detected in 17.65% cytologically normal/inflammatory patients, in 30% patients with ASCUS, 61.50% patients presenting LSIL and 70% patients with HSIL/cancer. hTERT mRNA expression was significantly increased in LSIL (p = 0.035) and HSIL/cancer (p=0.0044) as compared with normal group, but hTERT expression in ASCUS patients group does not present statistical significance as compared with the normal group (p=0.37). The association between the expressions of hTERT, the presence of hrHPV as well as dysplasia grade suggests that the hTERT activation may be a central mechanism by which HPV infections lead to malignant transformation. Analysis of hTERT expression can be used in diagnosis to decrease the false-negative cytology tests but only as an adjuvant, requiring correlation with the results of morphological feature.
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